Needle-free injection

Other delivery systems are transdermal patches, metered dose inhalers, nasal sprays, implantable devices, and needle-free injections. A description of needleless injection is given in Exhibit 5.16. 

Anwer, K., Earle, K.A., Shi, M., Wang, J., Mumper, R.J., Proctor, B. et al. (1999) Synergistic effect of formulated plasmid and needle-free injection for genetic vaccines. Pharm. Res., 16, 889-895. 

Needle-free injection is an intradermal drug delivery technology that can be considered as a hybrid of transdermal and parenteral technologies. The technology was first proposed in the early twentieth century... 

Powder injection applies many of the principles of pulmonary delivery of dry powders to the lungs The drug has to be in the form of very small particles, is dispensed from a reservoir, and is delivered as an aerosol i.e., particles are dispersed in a gas. Liquid or dissolved drug can be delivered by precipitation or adsorption onto carrier particles. The big difference with pulmonary delivery is the momentum at which the particles are delivered. Driven by a high-pressure helium gas stream, the particles travel fast enough to penetrate the outer layer of the skin, the stratum corneum. The design of devices to deliver needle-free injection of solids was pioneered by researchers at the University of Oxford who founded PowderJect Pharmaceuticals PLC in 1993 (now PowderMed Ltd.) to develop the only powder-based technology so far. Since that... 

Dry-powder inhalers (DPIs) deliver the drug to the respiratory tract in aerosol form. An aerosol is by definition a suspension of free liquid or solid fine particles in a gas phase, which is air in the case of DPIs (and a compressed gas in the case of needle-free injection). The most prominent characteristic that determines the delivery of drug particles to the lungs is the particle size, although particle shape and density are also of considerable importance for the behavior of an aerosol in the respiratory tract (Brain and Blanchard 1993 Gonda 1992 Heyder et al. 1986 Agnew 1984 Heyder et al. 1980). 

The unique form of needle-free injection of powders into the epidermis or mucosa has been developed by researchers at the University of Oxford and Powderject Pharmaceuticals PLC (now PowderMed Ltd., United Kingdom). Drugs in microparticulate form are accelerated to sufficient velocities to enter the skin or mucosa and achieve a therapeutic effect (Burkoth et al. 1999). Provided the drug particles are sufficiently small to avoid skin lesions and pain, the concept has been shown to be clinically effective, pain-free, and applicable to a range of therapies. Use is pain-free because the penetration depth of the particles is typically less than 100 J,m into the epidermis, and thus the sensory nerve endings lying in the papillary dermis usually are not excited (Fig. 8.15). 

Powder needle-free injection relies on being able to formulate particles of a sufficient density and accelerating them to a sufficient velocity that they will penetrate the skin in large enough numbers to produce a therapeutic dose. This is a challenging feat of engineering, especially if it is to be achieved without a notable supersonic boom. ... 

As previously described, liquid needle-free injection was the first needle-free technology to be developed and has been the focus of the vast majority of companies working in the industry. Indeed, many millions of... 

The key to achieving a successful injection with a needle-free system is to understand the necessary mechanics for the consistent penetration of skin and fat with a liquid jet, without causing unnecessary trauma to the tissues and to the molecule being delivered. Only recently have detailed studies of the fluid mechanics of needle-free injection appeared. The fluid mechanics conditions necessary for a consistent targeted needle-free injection are addressed in the following section. 

Even once the skin has been punctured, this does not guarantee a successful needle-free injection. There are several technical conditions that must be satisfied to ensure all the fluid is delivered into the subcutaneous layer. 

There are a wide variety of power sources available to designers of needle-free injection technology. There has... 

Fig. 1 Idealized needle-free injection pressure profile.

Table 1 Reports of needle-free injection containing clinical data...

Patient acceptability is another area that has seen significant developments in the last 10 years. Early needle-free devices were somewhat rudimentary in design and often used far more force to deliver the drug than was necessary. In addition to affecting pharmacokinetics, the excess force also led to a perception that needle-free injections are uncomfortable and inconvenient. Interestingly, despite various side effects and frequently poor performance (10-20% unsuccessful injections), needle-free presentations were still generally preferred by patients, although only around 70-85% preference was typically seen. " ... 

The needle-free injection field has evolved enormously in recent years. Companies have come and gone, taking with them some technologies. This section summarizes the technologies and the companies behind them that are currently active in the held. A review of some of the more prevalent technologies was published in 2002 while a more comprehensive list of companies that have developed needle-free injectors, for both human and veterinary use, is available at http / / www.cdc.gov/nip / dev/jetinject.htm. 

Algorx has the rights to develop the PowderJect needle-free injection technology in all areas outside of DNA vaccines. The device is helium powered and was described more fully earlier in this chapter. 

Potter, C. Caretek medical device. Management Forum Conference on Needle-Free Injection Systems and Auto-Injectors. Management Forum, London, England, Feb 23, 2004. 

Shergold, O.A. The Mechanics of Needle-Free Injection. Ph.D. thesis, Cambridge University, Cambridge, England, 2004. 

King, T. Needle-free injection protein delivery via pre-filled needle-free liquid injection. Drug Delivery Technol. 2003, 3 (7), 52-57. 

Cooper, J.A. Bromley, L.M. Baranowski, A.P. Barker, S.G.E. Evaluation of a needle-free injection system for local anaesthesia prior to venous cannulation. Anaesthesia 2000, 55, 247-250. 

Jackson, J. Dworkin, R. Tsai, T. McMullen, R. Kuchmak, N. Comparison of antibody response and patient tolerance of yellow fever vaccine administered by the Biojector needle-free injection system versus conventional needle/syringe injection. International Society of Travel Medicine Conference, Paris, 1993. 

Cui, Z. Baizer, L. Mumper, R.J. Intradermal immunization with novel plasmid DNA-coated nanoparticles via a needle-free injection device. J. Biotechnol. 2003, 102, 105-115. 

Needle-free injection Antares Pharma www.antarespharma.com... 

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